Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-β1 expression and fibrosis in minipigs with ischemia-reperfusion injury

Background  The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury.
Methods  Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n=5) or saline (control group, n=5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-β1 was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining.
Results  As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5±5.1) to (32.3±5.6) ml, P <0.05) and end-systolic volume (from (8.3±3.2) to (15.2±4.1) ml, P <0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6±13.3)% to (50.2±11.9)%, P <0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P <0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P <0.05). 
Conclusion  Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.